The application of the latest technologies to simultaneously measure the concentration of intracellular ions, as well as cell membrane potential together with myocardial cell rhythmicity is of central importance to advance the understanding of the pathophysiology of heart diseases. By so doing, novel approaches will be forthcoming for prophylactic and therapeutic intervention of heart disease. To address this need, a Myocardial Cell Analysis System (MCAS) will be developed. The MCAS is a non-disruptive, turnkey system that in real-time, simultaneously measures myocardial cell beat rate, cell membrane potential (or electrical activity) and a minimum of two intracellular ion concentrations (Na+ together with Cl-; or Ca2+ together with Cl-) in cardiac myocytes. The MCAS enables the above cellular functions to be measured either, a) in cultured myocytes using an inverted microscope (an in vitro MCAS-IV system), or b) in isolated perfused hearts using a coupling probe (an in situ MCAS-IS probe). In this Phase I project, a fiberoptic prototype will be developed utilizing fluorescence photon counting of ion sensitive fluorophores and heterodyne laser light scattering. Signal processing will include time-frequency and time-scale analyses (wavelet). This prototype MCAS will be calibrated and tested in cultured cardiac myocytes and in an in situ heart model. In Phase II, the MCAS will be packaged into a turn-key system that directly attaches to most commercial microscopes. PROPOSED COMMERCIAL APPLICATION This system will be used in investigating the cellular abnormalities of heart diseases. The system is also applicable to assess most types of biological motilities as well as intracellular ion dynamics of many cell types.